With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

OBJECTIVE: To identify prognostic genes associated with lysosome-dependent cell death (LDCD) in patients with gastric cancer (GC). METHODS: Differentially expressed genes (DEGs) were identified using The Cancer Genome Atlas - Stomach Adenocarcinoma. Weighted gene co-expression network analysis was performed to identify the key module genes associated with LDCD score. Candidate genes were identified by DEGs and key module genes. Univariate Cox regression analysis, and least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were performed for the selection of prognostic genes, and risk module was established. Subsequently, key cells were identified in the single-cell dataset (GSE183904), and prognostic gene expression was analyzed. Cell proliferation and migration were assessed using the Cell Counting Kit-8 assay and the wound healing assay. RESULTS: A total of 4,465 DEGs, 95 candidate genes, and 4 prognostic genes, including C19orf59, BATF2, TNFAIP2, and TNFSF18, were identified in the analysis. Receiver operating characteristic curves indicated the excellent predictive power of the risk model. Three key cell types (B cells, chief cells, and endothelial/pericyte cells) were identified in the GSE183904 dataset. C19orf59 and TNFAIP2 exhibited predominant expression in macrophage species, whereas TNFAIP2 evolved over time in endothelial/pericyte cells and chief cells. Functional experiments confirmed that interfering with C19orf59 inhibited proliferation and migration in GC cells. CONCLUSION C19orf59, BATF2, TNFAIP2, and TNFSF18 are prognostic genes associated with LDCD in GC. Furthermore, the risk model established in this study showed robust predictive power.
Stomach Neoplasms/pathology* ; Humans ; Prognosis ; Lysosomes/physiology* ; RNA-Seq ; Cell Death ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Cell Proliferation ; Single-Cell Gene Expression Analysis

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

Objective Cheng's Juanbi Decoction(CSJBD)is a classic traditional Chinese medicine formula for treating rheumatoid arthritis(RA),exhibiting significant clinical efficacy,but the underlying mechanisms remain unclear.We investigated whether CSJBD inhibited RA pathology by blocking the WTAP-Wnt7b-Wnt/β-catenin signaling axis using a collagen-induced arthritis(CIA)mouse model and fibroblast-like synoviocytes(FLSs)derived from RA patients(RA FLSs)and examined the underlying mechanisms.Methods We conducted in vivo experiments.Male C57BL/6 mice weighing 17 to 20 g were used to establish the CIA model.The mice were assigned to 6 groups,including the normal group,the model(CIA)group,the model+CSJBD-L(8.1 g/kg)group,the model+CSJBD-M(16.2 g/kg)group,the model+CSJBD-H(32.4 g/kg)group,and the model+leflunomide(LEF)(0.05 mg/10 g)group,with 10 mice in each group.CSJBD was administered twice daily via gastric gavage,while LEF was administered once daily via gastric gavage,for a duration of 28 days.We also conducted in vitro experiments.RA FLSs were assigned to 4 groups,including the RA FLSs+CSJBDS-L group receiving 10%CSJBDS-containing serum,the RA FLSs+CSJBDS-M group receiving 15%CSJBDS-containing serum,the RA FLSs+CSJBDS-H group receiving 20%CSJBDS-containing serum,and the RA FLSs+NC group(negative control).To study whether WTAP regulated Wnt7b,RA FLSs were divided into the RA FLSs group,the RA FLSs+si-WTAP#3 group,the RA FLSs+si-WTAP#3+Wnt7b-OE group,and the RA FLSs+si-WTAP#3+Wnt7b-NC group.To study the underlying mechanism by which CSJBT affected RA FLSs,RA FLSs were divided into the RA FLSs group,the RA FLSs+CSJBDS-M group,the RA FLSs+CSJBDS-M+Wnt7b-OE group,and the RA FLSs+CSJBDS-M+NC group.We used ultra-high performance liquid chromatography(UPLC)to identify and quantify key monomer compounds from CSJBD as quality criteria for CSJBD preparation.Bioinformatics,CCK-8,RT-qPCR,Western blot,immunofluorescence,and related methods were employed to assess the therapeutic efficacy and underlying mechanisms of CSJBD in treating RA.Results According to the UPLC analysis,ferulic acid,osthole,mulberroside A,notopterol,and gentiopicroside were identified as quality control standards for the preparation of CSJBD formula.CSJBD improved RA pathology in CIA mice,reduced the levels of interleukin(IL)-6,IL-1β,IL-8,and tumor necrosis factor-α(TNF-α)in their serum,and decreased the expression of RA pathological genes MMP3 and fibronectin,with the difference between groups being statistically significant.Bioinformatics analysis suggested that CSJBD might inhibit RA pathology by suppressing the Wnt/β-catenin signaling pathway through Wnt7b.Experimental results showed that the expression of WTAP and Wnt7b was significantly increased in RA.After knocking down WTAP,the expression of Wnt7b was significantly reduced,and the Wnt/β-catenin signaling pathway was also inhibited,with the difference between groups being statistically significant(P<0.05),confirming that WTAP regulated the pathway via Wnt7b.According to experimental verification,CSJBD significantly inhibited the Wnt/β-catenin signaling pathway and the proliferation of RA FLSs.Wnt7b overexpression reversed the inhibitory effect of CSJBD on the Wnt/β-catenin signaling pathway and the proliferation of RA FLSs,indicating that Wnt7b is the direct target of CSJBD.Conclusion CSJBD inhibits RA pathology by blocking the WTAP-Wnt7b-Wnt/β-catenin signaling axis,with Wnt7b identified as a direct therapeutic target of CSJBD.

Objective In this preliminary survey,we sought to determine the composition of mosquito species inhabiting the Emeifeng Nature Reserve,Fujian Province,China.Methods Mosquito larvae were collected by straw and spoon trapping,and adult mosquitoes were collected by lamp trapping at selected breeding sites in the reserve.The specimens were initially identified based on morphology,with subsequent verification using molecular biology methods.Results A total of 34 mosquito species in 13 genera were collected,among which,there were 4 species of Anopheles(Genus Anopheles Meigen,1818),2 species of Lutzia(Genus Lutzia Theobald,1903),15 species of Culex(Genus Culex Linnaeus,1758),4 species of Stegomyia(Genus Stegomyia Theobald,1901),and single species of Hulecoeteomyia(Genus Hulecoeteomyia Theobald,1904),Luius(Genus Luius Reinert,Harbach et Kitching,2008),Aedes(Genus Aedes Meigen,1818),Downsiomyia(Genus Downsiomyia Vargas,1950),Collessius(Genus Collessius Reinert,Harbach et kitching,2006),Uranotaenia(Genus Uranotaenia Lynch 1891),Armigeres(Genus Armigeres Theobald,1901),Toxorhynchites(Genus Toxorhynchites Theobald,1901),and pestle mosquito(Genus Tripteroides Giles,1904).Conclusions The species composition of mosquitoes sampled in the Emeifeng Nature Reserve will provide a basis for further research on mosquito vectors and contribute to measures for local mosquito control.

OBJECTIVE To explore the detoxification mechanism of Terminalia chebula Retz(TCR)soup-processed Euphorbia fischeriana Steud.(EFS)based on LC-MS and simulation processing.METHODS The changes of chemical composition of TCR soup-processed EFS,and dichloromethane extracts of crude EFS after simulation processing with TCR soup were analyzed by LC-MS.Mice were orally administered with alcoholic extracts of crude EFS,alcoholic extracts of water-processed EFS,alcoholic extracts of TCR soup,alcoholic extracts of TCR soup-processed EFS,dichloromethane extracts of crude EFS,dichloromethane extracts of TCR soup-processed EFS,and dichloromethane extracts of crude EFS after simulation processing with TCR soup,respectively.Toxicity changes in TCR soup-processed EFS and dichloromethane extracts of crude EFS after simulation processing with TCR soup were evalu-ated by fecal water contents,release levels of TNF-α and IL-1β,and intestinal pathology.RESULTS A total of 115 and 53 com-pounds were identified in EFS and TCR soup,respectively.The contents of 58 and 12 compounds significantly decreased and signifi-cantly increased respectively in EFS after processing with TCR soup.Compared to the blank control group,the fecal water contents and the release levels of TNF-α and IL-1β significantly increased in both the crude and water-processed EFS groups(P<0.01),and no-table intestinal injury was observed.Compared to the crude EFS group,the fecal water contents and the release levels of TNF-α and IL-1β significantly decreased in both the TCR soup group and the TCR soup-processed EFS group(P<0.01),and repaired intestinal injury was observed.After simulation processing for the dichloromethane extracts of crude EFS with TCR soup,the ion intensity change rates for diterpenoids and tannin phenolic acid compounds ranged from-6.75%to 8.09%and 66.06%to 100.00%,respectively.The ion intensity change rates of diterpenoids in the dichloromethane extracts of TCR soup-processed EFS ranged from-9.92%to 54.72%with almost no tannin phenolic acid compounds.Compared to the blank control group,the fecal water contents and the release levels of TNF-α and IL-1β significantly increased in both the dichloromethane extracts of crude and TCR soup-processed EFS groups(P<0.01),and severe intestinal injury was observed.Compared to the dichloromethane extracts of crude EFS group,the fecal water contents and the release levels of TNF-α and IL-1β significantly decreased in the group of the dichloromethane extracts of crude EFS after simulation processing with TCR soup(P<0.01),with no apparent intestinal injury.CONCLUSION TCR soup pro-cessing can alleviate the intestinal toxicity of EFS.The detoxification mechanism may involve the introduction of a large number of tan-nin phenolic acid compounds in TCR soup during the processing of EFS,which plays a pharmacological antagonistic role in the animal body.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.